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. 2025 Oct 14;54(6):dyaf190.
doi: 10.1093/ije/dyaf190.

Additive interactions of smoking with obesity on ischemic heart disease mortality: a national prospective cohort study in the United States

Yachen Zhu  1 , Carolin Kilian  2   3   4   5 , Julia Lemp  2   6 , Laura Llamosas-Falcón  2   7 , Charlotte Probst  2   7   8   9
Affiliations

Additive interactions of smoking with obesity on ischemic heart disease mortality: a national prospective cohort study in the United States

Yachen Zhu et al. Int J Epidemiol. .

Abstract

Background: Smoking and obesity are important modifiable risk factors for ischemic heart disease (IHD), often clustering within the same individuals. Previous US studies showed mixed findings regarding their interaction effects on IHD mortality and only investigated the question on the multiplicative scale, while additive scale is better suited to inform public health interventions.

Methods: We linked the 1997-2018 National Health Interview Survey data to the 2019 National Death Index. A total of 579 503 adults aged 18 years and older were included. Mortality status or last presumed alive was assessed until 31 December 2019. We used Aalen's additive hazards models and calculated the relative excess risk due to interaction (RERI) from Cox proportional hazards models and Fine-Gray subdistribution models that accounted for competing risks to comprehensively evaluate the interaction effect of smoking with obesity on IHD mortality.

Results: During 10.4 years of follow-up on average, 13 231 IHD deaths occurred. The weighted mortality rate was 177.0 (95% CI: 172.3-181.7) per 100 000 person-years (PY). The combination of current everyday smoking and obesity was associated with 55.56 (95% CI: 30.37-80.74) additional deaths per 100 000 PY compared to the sum of their individual effects. This additive interaction was supported by multiplicative interactions (HR = 1.19, 1.03-1.39; HR = 1.40, 1.22-1.59) and large RERIs of 1.00 (0.59-1.40) and 0.85 (0.6-1.09) from the Cox and Fine-Gray models, respectively.

Conclusions: Our findings highlight the importance of evaluating interactions on multiple scales, which reduces scale-dependence of the interaction effect and can translate better into public health strategies.

Keywords: additive interaction; ischemic heart disease mortality; multiplicative interaction; obesity; smoking.

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Conflict of interest statement

None declared.

References

    1. Ragland KE, Selvin S, Merrill DW. The onset of decline in ischemic heart disease mortality in the United States. Am J Epidemiol 1988;127:516–31. - PubMed
    1. Huisman M, Kunst AE, Mackenbach JP. Educational inequalities in smoking among men and women aged 16 years and older in 11 European countries. Tob Control 2005;14:106–13. - PMC - PubMed
    1. Roskam A-JR, Kunst AE, Van Oyen H et al. ; for Additional Participants to the Study. Comparative appraisal of educational inequalities in overweight and obesity among adults in 19 European countries. Int J Epidemiol 2010;39:392–404. - PubMed
    1. Nordestgaard BG, Palmer TM, Benn M et al. The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach. PLoS Med 2012;9:e1001212. - PMC - PubMed
    1. Barry J, Mead K, Nabel EG et al. Effect of smoking on the activity of ischemic heart disease. JAMA 1989;261:398–402. - PubMed